EFFECTS OF CAPTOPRIL THERAPY ON ENDOGENOUS FIBRINOLYSIS IN MEN WITH RECENT, UNCOMPLICATED MYOCARDIAL-INFARCTION

Objectives. This study investigated the effects of captopril therapy o n endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. Background. Angiotensin converting enzyme inhibitors redu ce the incidence of acute coronary syndromes in patients with mild lef t ventricular dysfunction after myocardial infarction, Abnormal endoge nous fibrinolysis, reflected in increased levels of endogenous tissue type plasminogen activator (t-PA) antigen and plasminogen activator in hibitor type 1 activity, is associated with an increased risk of myoca rdial infarction in patients with ischemic heart disease. Methods. In a randomized, double blind crossover study beginning 8 weeks after unc omplicated myocardial infarction, patients received 4 weeks of placebo and 4 weeks of captopril (75 mg daily) therapy. At the end of each tr eatment period, we measured t-PA antigen and plasminogen activator inh ibitor type 1 antigen and activity. Results. Median values in the 15 p atients after placebo and in 12 normal men matched for age and body ma ss index were, respectively, t-PA antigen 16.0 versus 9.5 ng/ml (p = 0 .001), plasminogen activator inhibitor type 1 antigen 17.3 versus 8.6 ng/ml (p = 0.29) and plasminogen activator inhibitor type 1 activity 1 3.2 versus 6.3 AU/ml (p = 0.04). After 4 weeks of treatment with capto pril in the 15 patients, the estimated (95% confidence interval) media n reduction in t-PA antigen was 7.3 ng/ml (-4.6 to -10.3 ng/ml, p = 0. 001), in plasminogen activator inhibitor type 1 antigen 3.1 ng/ml (+1. 5 to -8.4 ng/ml, p = 0.17) and in plasminogen activator inhibitor type 1 activity -2.2 AU/ml (-1.0 to -4.3 AU/ml, p = 0.02). Conclusions. Tr eatment with captopril after uncomplicated myocardial infarction is as sociated with a significant decrease in elevated levels of t-PA antige n and plasminogen activator inhibitor type 1 activity. This may help t o explain the reduction in risk of coronary thrombosis associated with the use of angiotensin-converting enzyme inhibitors.